OBJECTIVES : Genomic screening of the general population to identify breast and ovarian cancer-associated variants empowers women to choose prophylactic mastectomy and/or salpingo-oophorectomy prior to cancer development. However, reproductive considerations among others have been shown to impact the age of prophylaxis uptake, and older carriers may have already developed cancer prior to screening.

METHODS : We developed a de novo Markov model to compare screening versus no screening in an unselected/general population with a breast/ovarian cancer variant prevalence of 0.5%. The model included the following health states: no intervention/healthy, 1-cycle tunnel states for prophylactic surgeries, 1-cycle tunnel states for breast and ovarian cancer, post-surgical and post-cancer states, and death. The distribution of women in the first model cycle was determined by age-based cumulative incidences of (1) previous cancer and (2) previous prophylaxis uptake. Age-based estimates of variant-specific cancer incidence, uptake of prophylaxis, the costs of prophylactic procedures and cancer, and health state utilities were obtained from U.S. government and published sources. Test cost was $200, and we included a 1-year disutility (-0.05) for the psychological impact of receiving a positive screening result.

RESULTS : We estimated that screening resulted in 0.001 QALYs (95% CR: 0.0003 to 0.0012) gained at an incremental cost of $200 (95% CR: $60 to $450) for 30-year-olds (ICER = $264,000), and -0.0002 QALYs (95% CR: -0.00024 to -0.00011) lost at an incremental cost of $200 (95% CR: $50 to $450) for 50-year-olds.

CONCLUSIONS : The age at which women undergo screening for breast and ovarian cancer variants has important impacts on screening’s potential value, with younger women having a longer window to make reproductive and healthcare decisions. Screening for breast/ovarian cancer in older women may offer lower value in isolation, but its cost-effectiveness should be assessed within the context of a broader screening panel for other diseases.